The present invention relates to a liquid distribution system for chromatography columns. More specifically, the invention relates to a scalable liquid distribution system for large-scale chromatography columns.
In separation procedures, particularly in liquid chromatography, the fluid distribution system is critical to the overall performance, and becomes more so as the cross-section of the chromatographic column increases.
Columns used in liquid chromatography typically comprise a body-forming structure enclosing a porous media through which a carrier liquid flows, with separation taking place by material distribution between the carrier liquid and solid phase of the porous media. Typically, the porous media is enclosed in the column as a packed bed, typically formed by consolidating a suspension of discrete particles. An alternative to the packed bed is the so-called expanded or fluidised bed, where effective porosity and volume of the expanded bed depends on the fluid velocity. The term ‘packing’ shall be used in the following to describe the porous solid phase in all types of chromatography. The efficiency of the chromatographic separation relies in both modes strongly on the liquid distribution and collection system at the fluid inlet and outlet of the packing.
Ideally, the carrier liquid is uniformly introduced throughout the surface at the top of the packing, flows through the packing at the same linear velocity throughout the packing cross section, and is uniformly removed at the plane defined by the bottom of the packing.
Conventional distribution systems for use in liquid chromatography must address a number of inherent problems that have deleterious effects on the separation efficiency of the column. Among these problems is non-uniform initial fluid distribution at the top of the packing as well as non-uniform fluid collection at the outlet of the packing. The problem of non-uniform initial fluid distribution refers generally to the problem of applying a sample volume simultaneously over the cross-sectional area of the packing. Without a simultaneous introduction of fluid in the plane defined by the top of the packing, it is virtually impossible to achieve uniform flow distribution through the packing.
This will lead to increased dispersion in the chromatographic system by broadening the convective residence time distribution of a tracer substance transported with the fluid throughout the system. The dispersion generated by the liquid distribution system has to be controlled in relation to the amount of dispersion introduced by the chromatographic packing itself by means of diffusion and mixing effects.
Standard fluid distribution systems consist of one central inlet, formed in the end plate of the column, for the mobile phase in combination with a thin distribution channel (gap) behind the filter (woven net or sinter) or bed support at the inlet end of the column and a similar fluid collection system at the outlet end of the column. The filter or bed support is supported by ribs which extend from the inner surface of the end plate to side of the filter or bed support facing the end plate. The ribs extend radially and the spaces between the ribs form distribution channels for distributing the fluid. Each rib has a tapered end section facing the centre of the column and a body of substantially constant width extending from the tapered section to the wall of the column. At given radial positions, the number of ribs doubles in order to maintain the necessary mechanical support of the filter/bed support. In columns, the local effective cross-sectional area for fluid flow in the distribution channels at a radial position r is defined by the depth of the channels h, the width of the channels w and the number of channels. The local effective channel height (i.e. the height at a location at a given radial distance from the centre of the column) for fluid flow in a column is defined as the local height of a corresponding open channel (i.e. a rib-free channel) having the same cross-sectional area for fluid flow as the total cross-sectional area of the channels in the actual column at the same radial distance. Thus, if in a particular column the channel height at a distance R from the column centre was 4 mm and half of the cross-sectional area was occupied by ribs at distance R, then the effective channel height at distance R would be 2 mm. It is considered desirable that the local effective channel height varies linearly from the centre of the column to the column wall in order to give the desired fluid distribution over the filter or bed support. However, in the prior art, no account has made of the effect that the size and number of ribs has on the local effective channel height. This can be seen in FIG. 3 in which the solid line shows the calculated effective channel height (ECH) against radial distance (R) from the centre of the column for a typical prior art column with ribs starting at R=55 mm and R=110 mm, while the dotted line shows the desired linear variation in local effective channel height. At R=55 mm the actual local effective channel height is 3.2 mm while the desired local effective channel height is 3.8 mm, i.e. only 84% of the desired value, and at R=112 mm the actual local effective channel height is 1.4 mm—only 56% of the desired height is 2.5 mm. Clearly, there is a local decrease in the effective channel height, and therefore throttling of the flow in the distribution channels, at the radial positions where the number of ribs doubles. This causes a local pressure increase which has a negative impact on the chromatographic performance.